On July
22, 2010, the European Medicines Agency recommended restricting the use of modafinil.
Doctors and patients should be advised to use the drug only for the treatment
of narcolepsy and all other indications should be withdrawn from market
authorization, the press release said.

In
addition to the brand-name, Provigil, marketed by Cephalon in the US, modafinil
is also sold as Alertec, Modalert, Modavigil, Modiodal, Provake, and Vigil.

A review by the Agency's Committee for
Medicinal Products for Human Use (CHMP), began in May 2009, because of safety
concerns relating to psychiatric disorders, such as suicidal thoughts,
depression, and psychotic episodes, and life threatening skin
reactions, as well as significant off-label use and potential for abuse.

CHMP looked at all the clinical trial data
on modafinil for narcolepsy, obstructive sleep apnoea, shift-work sleep
disorder and idiopathic hypersomnia, and articles from the published
literature. CHMP also reviewed all the side effects reported on
modafinil-containing medicines, and convened a group of experts on clinical
neurosciences to provide advice, according to a Q&A document on EMA's
website.

On the basis of the available data, CHMP concluded that the benefits of
modafinil only outweighed the risks in treating narcolepsy and the clinical
trials for other disorders did not provide strong evidence to support use of
the drug. For other indications,
CHMP found the data on effectiveness insufficient to outweigh the risks of skin
reactions, psychiatric adverse reactions, and cardiovascular adverse reactions, such as
hypertension and irregular heart beat.

CHMP
concluded that the product information should carry a recommendation saying
modafinil should not be prescribed to children and use of the drug be
contraindicated in patients with uncontrolled moderate-to-severe hypertension
and cardiac arrhythmias. The recommendations were forwarded to the European
Commission for the adoption of a binding decision, the press release said.

Because CHMP noted
in its review that modafinil has often been used for conditions not indicated,
the drug makers were asked to carry out further studies, including a "drug
utilisation study," to look at why family doctors prescribe the drug, according
to the Q&A. In addition, data on misuse by university students is currently
being collected and will be analyzed once available, the EMA reports.

The
Medicines and Healthcare product Regulatory Agency issued a "stop
press" notice in the August 2010 edition of "Drug Safety
Update," reminding healthcare professionals of the EMA's recommendations.

US Market

Provigil was
approved for narcolepsy in late 1998, which only
affects around 200,000 people in the US, according to a July 2010 report by
Global Industry Analysts.

US
sales began in February 1999.Ten months later, "25% of narcolepsy
patients in the country, more than 31,000 people, were taking the drug. It
generated $25 million in 1999 sales, and Cephalon's revenue nearly tripled to
$45 million," according to an August 1, 2000 report, by Matthew Herper, on
Forbes.com.

A
November 20, 2002, New York Times article reported that Cephalon CEO, Frank
Baldino, himself, was taking Provigil, but would not say what condition he used
it for. Provigil is short for "promotes vigilance," according to the
Times.

Use of the drug is "expanding rapidly, with
more than 80 percent of the prescriptions written to treat the fatigue and
sleepiness associated with many other diseases, like depression and multiple sclerosis,
or even just sleepiness caused by no disease at all," the article reported
in 2002.

At that time, Baldino denied that the drug was or
would be abused. "I don't think it's going to happen, because we're
careful about how we sell it and doctors are careful how they write
prescriptions," he told the Times.

"He added that the growing use of the drug for
conditions other than narcolepsy is being driven by physicians, not by Cephalon's
marketing," the article said.

Less
than eleven months earlier, the FDA had sent a letter warning Cephalon to quit
promoting Provigil for off-label uses. The FDA objected to language indicating
the drug could be used for symptoms such as sleepiness, tiredness, decreased
activity, lack of energy and fatigue. "Provigil is indicated to improve
wakefulness in patients with excessive daytime sleepiness associated with
narcolepsy. Provigil is not approved for use as a daytime stimulant," the
FDA wrote in January 2002.